Many human small cell lung carcinomas make peptide hormones in the patient and in tissue culture cell lines derived from biopsy specimens. Two of these peptide hormones, arginine vasopressin (AVP) and bombesin/gastrin releasing peptide (GRP) appear to stimulate lung cancer cell growth under certain culture conditions. Other recent advances in oncogene research have shown that some oncogenes may be related to growth factors or their receptors. C-sis encodes a product with areas of homology to PDGF, and similarly the presumed product of erb-B may be related to the EGF receptor. To understand better the mechanism and importance of peptide hormone expression in small cell lung cancer cells, we are studying the structure and function of peptide hormone polyprotein genes and analyzing their expression in small cell tissue culture lines. We have obtained genomic clones of human AVP and oxytocin (OT) genes and determined their structures and nucleotide sequence. RNA blot analysis and S1 nuclease protection experiments have documented the mRNA initiation sites and probable promoter region for three forms of the mRNA transcribed in this cell. In addition, we have obtained a human genomic clone for the pro-opiomelanocortin (POMC) polyprotein gene which encodes the peptide hormones ACTH, MSH, and lipotropin. Several small cell lung cancer lines produce POMC mRNA, and we are presently characterizing the structure of this transcription unit and comparing it to the normal mRNA made in the anterior pituitary.